Service d'Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfants Malades, APHP, Paris, France.
Paris Sorbonne Cité, Université Paris Descartes, Paris, France.
Birth Defects Res. 2018 Apr 17;110(7):598-602. doi: 10.1002/bdr2.1204. Epub 2018 Jan 22.
The RTTN gene encodes Rotatin, a large centrosomal protein involved in ciliary functions. RTTN mutations have been reported in seven families and are associated with two phenotypes: polymicrogyria associated with seizures and primary microcephaly associated with primordial dwarfism.
A targeted exome sequencing of morbid genes causing cerebral malformations identified novel RTTN compound heterozygous mutations in a family where three pregnancies were terminated because a severe fetal microcephaly was diagnosed. An autopsy performed on the second sib showed moderate growth restriction and a microcephaly with simplified gyral pattern. The histopathological study discovered a malformed cortical plate.
The present study confirms the involvement of RTTN gene mutations in microcephaly with simplified gyral pattern and describes the observed abnormal neuropathological findings.
RTTN 基因编码 Rotatin，一种参与纤毛功能的大型中心体蛋白。已有七家报道 RTTN 基因突变，并与两种表型相关：伴有癫痫的多小脑回畸形和伴有原始侏儒症的原发性小头畸形。
对导致脑畸形的致病基因进行靶向外显子组测序，在一个因严重胎儿小头畸形而终止妊娠的家庭中发现了 RTTN 复合杂合突变。对第二个同胞进行的尸检显示出中度生长受限和伴有简化脑回模式的小头畸形。组织病理学研究发现皮质板畸形。
本研究证实了 RTTN 基因突变在伴有简化脑回模式的小头畸形中的作用，并描述了观察到的异常神经病理学发现。
